The Linker Approach

This chapter evaluates the concepts of drug conjugation by discussing the different types of drug conjugates as well as the chemistry of their linkers and by gathering available clinical data for drug conjugates. Linkers can generally be divided into cleavable and non-cleavable. Small molecule drug conjugates link two small molecules with defined molecular targets in one molecule. Conjugation of therapeutic antibodies to small molecule drugs constitutes the most prominent strategy in drug conjugation at present. The use of antibody-drug conjugates as targeted agents that predominantly release their cytotoxic load in cancer cells enables the application of drugs that alone have shown too high toxicity to be used as therapeutic agents. The potential of therapeutic proteins to exhibit immune-sensitizing effects can be reduced by conjugation to a polymer. The polymer-drug conjugate-based combination therapy opens new opportunities in the development of personalized medicines and could strengthen the progress of individualized therapies.